1. Field of the Invention
The present invention relates to the field of life support systems. In particular, the present invention relates to the field of ventilation systems and methods.
2. Description of the Related Art
For over forty years, mechanical ventilators have been one of the most important life-support systems for the treatment of respiratory failure. These mechanical ventilators have been designed to provide a predetermined volume of air for each breath. The volume of air being based upon a patient's weight and sometimes height. Although it is known that following a long period of mechanical ventilation in certain types of pre-existing lung disease some form of mechanical damage to the lungs can develop, the basic protocols of mechanical ventilation have not significantly changed. Many experimental studies have reported that patients with acute lung injury associated with acute respiratory distress syndrome (ARDS) are particularly at risk of ventilator-induced lung injury and subsequent worsening of their condition.
A significant problem in acute respiratory distress syndrome is that at the end of an expiration alveolar regions collapse with a concomitant impairment in gas exchange. To recruit these collapsed regions, ventilation is usually superimposed on a positive end-expiratory pressure (PEEP). Superimposing breaths on top of PEEP to improve gas exchange unfortunately has adverse effects on lung stretching, and tends to cause high peak airway pressures. The lung tissue then becomes over-distended. As a consequence, micro-vascular permeability increases due to endothelial cell damage which, in turn, causes alveolar and peribronchial edema and, perhaps in later stages, protein influx into the alveolar gas exchange region hindering oxygen uptake. To avoid these problems, the use of a combination of positive end-expiratory pressure sufficient to keep most airways open and low tidal volume to reduce distention at the end of each breath ventilation has been suggested to improve oxygenation at the expense of some deterioration in carbon dioxide elimination. However, several problems arise. First, because of CO2 accumulation, respiratory acidosis may develop leading to serious clinical complications. Second, if the positive end-expiratory pressure is not sufficiently high, regions in the periphery of the lung will still be prone to collapse toward end-expiration. During ventilation, these regions may repeatedly undergo opening and closing and hence extreme high shear stresses can develop along the airway walls. Thus, if the same region repeatedly collapses and reopens many times, the non-physiological shear forces will eventually lead to damaging the epithelial cell layer causing protein influx into the alveoli and stress-induced cytokine expression. This initiates a self propagating state of mechanically activated inflammation. Third, while low tidal volume ventilation reduces mortality in ARDS, it does not eliminate it.
Thus, a delicate balance of positive end-expiratory pressure and tidal volume is needed to achieve the least injurious ventilation protocol and the best blood gas levels and this balance has to be continuously monitored and updated. Furthermore, in certain instances, some regions of lung will experience optimal conditions of ventilation in which shear stress is minimized, while adjacent more severely injured regions will experience ventilator-induced injury. Due to these difficulties, there has been little consensus on what strategy would be optimal in reducing the risk of ventilator-induced lung injury.
In 1996 Lefevre et al. introduced “biologic variability” into mechanical ventilation as a potential alternative to conventional mechanical ventilation (G. R. Lefevre, J. E. Kowalski, L. G. Girling, O. B. Thiessen, and W. A. C. Mutch, Am. J. Respir. Crit. Care Med., 154, 1567-1572 (1996)). Lefevre et al. pointed out that while spontaneous variability of all physiologic rhythms are essential features of living organisms, conventional life-support systems eliminate this inherent variability. They introduced a computer-controlled ventilator such that the tidal volume was taken from a Gaussian distribution and the respiratory rate was adjusted to keep minute ventilation constant. They found that, in a pig model of oleic acid induced lung injury, arterial blood gases improved significantly using this computer-controlled ventilation mode compared to conventional ventilation. Lefevre et al. termed their ventilation mode “biologic variability” because their frequencies mimic the variability of natural breathing frequency.
Nevertheless, Lefevre et al did not offer any mechanistic explanation for their findings. In two subsequent studies, Mutch and colleagues expanded their work to show that this ventilation mode works over longer ventilation periods and using positive end-expiratory pressure.